The goal of this research is to characterize cell membrane antigens recognized by a panel of monoclonal antibodies which bind specifically to mouse osteoblasts, especially those antigens which are associated with the function of the parathyroid hormone (PTH) receptor. Antibodies which bind specifically to osteoblasts, as determined by histology and flow cytometry, will be surveyed. The ability of antibodies to influence PTH receptor activities will be examined in cultured mouse bone and isolated populations of mouse bone cells. Activities to be examined include binding of PTH and labeled PTH analogs, activation of adenylate cyclase, suppression of alkaline phosphatase and induction of bone resorption. Antigens associated with the osteoblast PTH receptor will be isolated by immunoaffinity techniques and further characterized biochemically. Antibodies which these experiments indicate are specific for components of the PTH receptor system will be used to screen recombinant expression libraries for nucleotide sequences coding for the relevant antigens, with the objective of determining the complete cDNA sequence of osteoblast PTH receptors. Both the antibodies and the isolated nucleic acid probes will be used to evaluate expression of the PTH receptor gene(s) in osteoblasts and related cells. These investigations will provide detailed information about the unique characteristics of bone cell surfaces and the molecular processes involved in PTH action. This knowledge will allow a better understanding of changes in bone cell function in a number of bone-related diseases including osteoporosis, rheumatoid arthritis, pseudohypoparathyroidism and neoplastic bone destroying conditions.